Staphylococcus aureus is a bacterial pathogen responsible for a wide range of diseases and conditions, ranging from minor skin infections to serious life-threatening wound infections, bacteraemia, endocarditis, pneumonia, osteomyelitis and toxic shock syndrome. While S. aureus commonly colonizes in the nose and skin of healthy humans, often causing only minor infections (e.g., pimples, boils), it can also cause systemic infections. Examples of diseases and conditions caused by S. aureus include bacteremia, infective endocarditis, folliculitis, furuncle, carbuncle, impetigo, bullous impetigo, cellulitis, botryomyosis, toxic shock syndrome, scalded skin syndrome, central nervous system infections, infective and inflammatory eye disease, osteomyelitis and other infections of joints and bones, and respiratory tract infections. (The Staphylococci in Human Disease, Crossley and Archer (eds.), Churchill Livingstone Inc. 1997; Archer, 1998, Clin. Infect. Dis. 26:1179-1181.)
Staphylococcus aureus is a nosocomial as well as a community-acquired pathogen which causes several diseases ranging from. See Lowy et al., 1998, N. Engl. J. Med. 339:520-32. The worldwide growing incidence of staphylococcal infections is strongly related to the increased use of surgical devices and a growing number of immunocompromised patients. The situation has become more serious since the increased use of antibiotics led to the emergence of methicillin-resistant S. aureus strains (MRSA). See Selvey et al., 2000, Infect. Control. Hosp. Epidemiol. 21:645-8; Peacock et al., 1980, Ann. Intern. Med. 93:526-32. Additionally, S. aureus isolates with reduced susceptibility to vancomycin, the antibiotic of choice against MRSA strains, were described in the lab as well as the clinic See Tenover et al., 2001, Emerg. Infect. Dis. 7:327-32; Tenover et al., 1998, J. Clin. Microbiol. 36:1020-7; Palazzo et al., 2005, J. Clin. Microbiol. 43:179-85. The rising emergence of multidrug-resistant staphylococci has led to a growing interest in the development of alternative approaches to prevent and treat staphylococcal infections.
Information concerning S. aureus polypeptide sequences has been obtained from sequencing the S. aureus genome. See Kuroda et al., 2001, Lancet 357:1225-1240; Baba et al., 2000, Lancet 359:1819-1827; Gill et al., 2005, J. Bacteriol. 187:2426-2438 and European Patent Publication EP 0 786 519. To some extent, bioinformatics has been employed in efforts to characterize polypeptide sequences obtained from genome sequencing. See, e.g., European Patent Publication EP 0 786 519 and U.S. Pat. No. 6,593,114.
Techniques such as those involving display technology and sera from infected patients have also been used in an effort to help identify genes coding for potential antigens. See, e.g., International Publication Nos. WO 01/98499 and WO 02/059148; and Etz et al., 2002, Proc. Natl. Acad. Sci. USA 99:6573-6578. Numerous staphylococcal surface proteins have been identified so far using recently adopted technologies, like proteomics (see Brady et al., 2006, Infect. Immun. 74:3415; Gatlin et al., 2006, Proteomics 6:1530; Pieper et al., 2006, Proteomics 6:4246; Vytvytska et al., 2002, Proteomics 2:580; Nandakumar et al., 2005, J. Proteome Res. 4:250) or protein selection methods based on expression libraries (see Clarke et al., 2006, J. Infect. Dis. 193:1098; Etz et al., 2002, Proc. Natl. Acad Sci. USA 99:6573-8; Weichhart et al., 2003, Infect. Immun. 71:4633; and Yang et al., 2006, Vaccine 24:1117).
Vaccines consisting of one or more antigenic determinants can provide protection against lethal challenge with S. aureus in mice. See Stranger-Jones et al., 2006, Proc. Natl. Acad. Sci. USA 103:16942-7 and Kuklin et al., 2006, Infect. Immun. 74:2215. Recombinantly expressed polypeptides can readily be made, purified, and formulated as vaccines. Additionally, recombinant proteins can be combined with additional components to make multicomponent polypeptide vaccines that induce a spectrum of immune responses. Despite this, there are no reported protein based vaccines for staphylococcal infections in humans or animals to date. Thus, there remains a need for immunogens that can provide protective immunity against Staphylococcal infections in human and/or animals.